This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Respiratory distress syndrome (RDS) is the most common pulmonary pathology in extremely low birth weight (ELBW) infants. In recent years there has been an increased use of nasal continuous positive airway pressure (nCPAP) in the management of ELBW infants with RDS. The use of early nCPAP eliminates the need for intubation and mechanical ventilation, and their associated morbidities. In clinical practice a significant number of ELBW infants with RDS fail nCPAP therapy within the first 72 hours of life and require rescue intubation. Prior studies using heliox (mixture of helium and oxygen) in the management of RDS have shown clear therapeutic benefits. The use of heliox delivered via a nCPAP device (Hx-nCPAP) has recently been reported. Given the prior success of heliox in the management of RDS combined with the recent advent of Hx-nCPAP we intend to investigate the utility of Hx-nCPAP in reducing early nCPAP failure in ELBW infants with RDS. Research Design: Prospective, open-label, randomized, control trial comparing conventional nCPAP to Hx-nCPAP. Methods: Spontaneously breathing ELBW infants born at less than or equal to 28 wks estimated gestational age with RDS and on nCPAP since birth will be eligible for enrollment. Volunteer infants will be randomly assigned to conventional nCPAP or Hx-nCPAP. Primary and secondary outcome measures will be compared between the heliox group and control group to determine if Hx-nCPAP results in fewer early nCPAP failures and/or improved clinical outcomes. CRC involvement will include assistance with study coordination, subject recruitment, maintenance of study records, database creation, data entry, and data analysis.